Biological lipids assemble to form many different kinds of structures. Phospholipids, for example, form the roughly planar bilayer portions of biological membranes and vesicles, as also the small bile salt-lecithin mixed micelles in the bile. These lipid assemblies solubilize many physiological and exogenous substances. The objectives of this proposal are to study, in a comparative manner, the interfacial microenvironments of short-chain lecithin and lysolecithin micelles and unilamellar vesicles of long-chain lecithins, and to correlate such studies with the nature of the interactions of small molecules with such organized structures. The approaches to be used have been tested for detergent micelles. Indications are that the phosphatidylcholine dipolar head groups and interfacial curvatures are likely to be important factors. The interfacial polarity will be studied by using the solvent-sensitive interionic charge-transfer spectra of alkyl pyridinium iodides. Its effect on the dissociation constants of acidic and basic groups will be studied using indicator dyes. An ultraviolet spectroscopic method will be used to study the microenvironments of benzene derivatives and naphthalene and attempts will be made to extend the method to polycyclic hydrocarbons. Molecules containing the nitroxide spin label will be similarly investigated using a highly solvatochromic visible absorption band. Micellar studies have shown that the interfacial activities of some solutes at the dodecane-water interface are closely related to their locations in the micelles and the solvent power of the micelles. Such studies will be extended to other solutes. The results are likely to be of significance in the understanding of transport, lipid-binding, and chemical-metabolic reactivities of many physiological substances, anesthetics, drugs, toxicants and carcinogens, and a critical appraisal of the assumptions behind the use of some spectroscopic probes for lipid assemblies.